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Author: 廖證傑
Liao, Cheng-Chieh
Thesis Title: 雙功能金雞納鹼催化3-高醯基香豆素與亞甲基羥吲哚進行不對稱麥可-麥可反應建構螺環羥吲哚
Bifunctional Cinchona Alkaloid-Catalyzed Asymmetric Cascade Michael-Michael Reaction of 3-Homoacyl Coumarin with Methyleneoxindoles the Construction of Spirooxindoles
Advisor: 林文偉
Lin, Wen-Wei
Degree: 碩士
Master
Department: 化學系
Department of Chemistry
Thesis Publication Year: 2019
Academic Year: 107
Language: 中文
Number of pages: 340
Keywords (in Chinese): 連鎖反應麥可/麥可反應螺環羥吲哚
Keywords (in English): cascade reaction, Michael/Michael reaction, spirooxindole
DOI URL: http://doi.org/10.6345/NTNU201900072
Thesis Type: Academic thesis/ dissertation
Reference times: Clicks: 129Downloads: 0
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螺環羥吲哚(spiroxindole)是一種特殊的骨架,出現於天然物及藥物中都很普遍,且報導指出其具有生物活性,使得化學家相繼進行深入研究。本實驗證明利用金雞鈉鹼(Cinchona alkaloid)衍生物催化羥吲哚(oxindole)衍生物,與3-高醯基香豆素(3-homoacyl coumarin)衍生物進行分子間及分子內的Michael reaction,以建構螺環羥吲哚,獲得五個相鄰的立體中心具良好產率及鏡像選擇性;同時設計起始物羥吲哚衍生物,取代基苯基(phenyl)及苯甲醯基(benzoyl group),推測在羰基(carbonyl)存在下,利用氫鍵的控制,增加選擇性,使得在優化條件下,成功得到更佳優良的鏡像選擇性。

The spirooxindole structure is a privileged scaffold that is prevalent in both natural products and synthetic bioactive molecules. Herein, we demonstrate a Cinchona alkaloid derivative catalyzed Michael/Michael cascade reaction of 3-homoacyl coumarins and arylidene or benzoylated oxindoles to construct spirooxindole derivatives. This reaction afforded the corresponding products with five contiguous stereocenters including a quaternary center in good to excellent yields with moderate to excellent enantioselectivities. The comparision between the substitutent on oxindole ring phenyl and benzoyl group, the benzoyl group has carbonyl group it shows the different results and catalyst because of the hydrogen bonding.

摘要.......I Abstract.......II 謝誌.......III 目錄.......IV 圖目錄.......VI 反應式目錄.......VIII 表目錄.......X 縮寫用語對照表.......XI 壹、緒論....... 1 (一) 前言.......1 (二) 研究動機....... 5 1. 1,3-雙偶極體 (3+2) 合環反應.......5 2. 全碳合環反應策略.......12 3. 金雞鈉鹼催化劑演化.......18 4. 透過有機催化合成螺環羥吲哚.......25 (三) 分子設計.......30 貳、結果與討論.......33 (一) 苯基.......33 1. 外消旋混合物條件篩選.......33 2.掌性催化劑篩選.......34 3.掌性環境下保護基及溶劑篩選.......37 4.反應環境條件篩選.......38 5.取代基效應.......39 6.控制實驗.......42 7.絕對立體組態.......43 8.反應機制探討.......43 (二) 苯甲醯基.......45 1.掌性催化劑篩選.......45 2.溶劑篩選.......47 3.反應環境條件篩選.......47 4.反應當量篩選.......48 5.取代基效應.......49 6.絕對立體組態.......51 7.控制實驗及機制推論.......52 (三) 克級反應.......54 參、結論....... 55 肆、未來展望.......56 1.實驗衍生化.......56 2.有機磷化學研究.......57 伍、實驗步驟.......58 (一)一般實驗方法.......58 (二) 實驗步驟.......60 (三) 實驗數據.......65 參考文獻.......109 附錄一、氫核磁共振光譜圖、碳核磁共振光譜圖、高解析質譜圖、高液相層析圖.......112 附錄二、X-ray 單晶繞射結構解析.......292

1. Xue, Y.-P.; Cao, C.-H.; Zheng, Y.-G.* Chem. Soc. Rev. 2018, 47, 1516.
2. Wu, Y.-F.; Tsai, Y.-F.;* Guo, J.-R.; Yu, C.-P.; Yu, H.-M.* Liao, C.-C. Org. Biomol. Chem. 2014, 12, 9345.
3. Donovan, K. A.; An, J.; Nowak, R. P.; Yuan, J. C.; Fink, E. C.; Berry, B. C.; Ebert, B. L.; Fischer, E. S.;* eLife 2018, 7, e38430.
4. Cheng, D.; Ishihara, Y.; Tan, B.;* Barbas, C. F.* ACS Catal. 2014, 4, 743.
5. Chen, X.; Duan, S.; Tao, C.; Zhai, H.;* Qiu, F. G.* Nat. Commun. 2015, 6, 7204.
6. Onishi, T., Sebahar, P. R., Williams, R. M.* Org. Lett. 2003, 5, 3135.
7. Kato, H.; Yoshida, T.; Tokue, T.; Nojiri, Y.; Hirota, H.; Ohta, T.; Williams, R. M.; Tsukamoto, S* Angew. Chem. 2007, 119, 2304.
8. Wang, Y.-H.; Avula, B.; Nanayakkara, N. P. D.; Zhao, J.; Khan, I. A.* J. Agric. Food Chem. 2013, 61, 4470.
9. Yao, P.-H.; Kumar, S.; Liu, Y.-L.; Fang, C.-P.; Liu, C.-C.; Sun, C.-M.;* ACS Comb. Sci. 2017, 19, 271.
10. Zhang, Z.-R.; Leung, W.N.; Cheung, H.Y.; Chan, C.W.* Evidence-Based Complementary and Alternative Medicine 2015, 2015, 919616.
11. Yang, N.-N.; Shi, H.; Yu, G.; Wang, C.-M.; Zhu, C.; Yang, Y.; Yuan, X.-L.; Tang, M.; Wang, Z.-L.; Gegen, T.; He, Q.; Tang, K.; Lan, L.; Wu, G.-Y.d;* Tang, Z.-X.* Scientific Reports 2016, 6, 25657.
12. Nagao, K; Yamano, N.; Shirouchi, B.; Inoue, N.; Murakami, S.; Sasaki, T.; YanagitaA, T.* J. Agric. Food Chem. 2010, 58, 9028.
13. Simijonović, D.;* Vlachou, E.-E.; Petrović, Z. D.; Hadjipavlou-Litina, D. J.; Litinas, Κ. E.; Stanković, N.; Mihović, N.; Mladenović, M. P. Bioorganic Chemistry 2018, 80, 741.
14. Huisgen, R.* Angew. Chem. Int. Ed. 1963, 11, 633.
15. Hashimoto, T.;* Maruoka, K.* Chem. Rev. 2015, 115, 5366.
16. Fukui, K.;* Yonezawa, T.; Shingu, H. J. Chem. Phys. 1952, 20, 722.
17. Sustmann, R.* Pure Appl. Chem. 1974, 40, 569.
18. Hashimoto, T.;* Maruoka, K.* Chem. Rev. 2015, 115, 5366.
19. Kobayashi, S.;* Kawamura, M. J. Am. Chem. Soc. 1998, 120, 5840.
20. Yamamoto, H.;* Jiao, P.; Nakashima, D. Angew. Chem. Int. Ed. 2008, 47, 2411.
21. Mondal, M.; Wheeler, K. A.; Kerrigan, N. J.;* Org. Lett. 2016, 18, 4108.
22. Wang, X.; Yang, P.; Zhang, Y.; Tang, C.-Z.; Tian, F.; Peng, L.; Wang, L.-X.;* Org. Lett. 2017, 19, 646.
23. Esteban, F.; Cieślik, W.; Arpa, E.M.; Guerrero-Corella, A.; Díaz-Tendero, S. ; Perles, J.; Fernández-Salas, J. A.; Fraile, A.;* Alemán, J.* ACS Catal. 2018, 8, 1884.
24. Chen, X.-H.; Wei, Q.; Luo, S.-W.; Xiao, H.; Gong, L.-Z.* J. Am. Chem. Soc. 2009, 131, 13819.
25. Kolb, H. C.; Finn, M. G.; Sharpless, K. B.* Angew. Chem. Int. Ed. 2001, 40, 2004.
26. Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.* Angew. Chem. Int. Ed. 2002, 41, 2596.
27. Krasin´ski, A.; Radic, Z.; Manetsch, R.; Raushel, J.; Taylor, P.; Sharpless, K. B.; Kolb, H. C.* J. Am. Chen. Soc. 2005, 127, 6686.
28. T. M. V. D. Pinho e Melo, Curr. Org. Chem. 2009, 13, 1406.
29. Du, Y.; Lu, X.;* Yu, Y. J. Org. Chem. 2002, 67, 8901.
30. Liu, C.; Oblak, E. Z.; M. N.; Vander Wal, M.N.; Dilger, A. K.; Almstead, D. K.; MacMillan, D. W. C.* J. Am. Chem. Soc. 2016, 138, 2134.
31. Marx, V. M.; Jean Burnell, D.* J. Am. Chem. Soc. 2010, 132, 1685.
32. Trost, B. M.; Huang, Z.; Murhade, G. M.* Science 2018, 362, 564.
33. Giese, S.; Kastrup, L.; Stiens, D.; West, F. G.* Angew. Chem. Int. Ed. 2000, 39, 1970.
34. Zhang, G.; Zhang, L.;* J. Am. Chem. Soc. 2008, 130, 12598.
35. Sun, M.; Zhu, Z.-Q.; Gu, L.; Wan, X.; Mei, G.-J.; Shi, F.* J. Org. Chem. 2018, 83, 2341.
36. Zhou, J.; Wang, Q.-L.; Peng, L.; Tian, F.; Xu, X.-Y.;* Wang, L.-X.* Chem. Commun. 2014, 50, 14601.
37. Song, C.E. (2009) Cinchona Alkaloids in Synthesis and Catalysis: Ligands, Immobilization and Organocatalysis.
38. Helder, R.; Arends, R.; Bolt, W.; Hiemstra, H.; Wynberg, H.* Tetrahedron Lett. 1977, 18, 2181.
39. Houk, K.N.;* Grayson, M.N. J. Am. Chem. Soc. 2016, 138, 1170.
40. Okino, T.; Hoashi, Y.; Furukawa, T.; Xu, X.; Takemoto, Y.* J. Am. Chem. Soc. 2005, 127, 119.
41. McCooey, S. H.; Connon, S. J.;* Angew. Chem. Int. Ed. 2005, 44, 6367.
42. Breman, A. C.; Heijden, G. V. D.; Maarseveen, J. H. V.; Ingemann, S.; Hiemstra, H.* Chem. Eur. J. 2016, 22, 14247.
43. Hine, J.;* Chen, Y.-J. J. Org. Chem. 1987, 52, 2091.
44. Albertshofer, K.; Tan, B.; Barbas, C.F.III.* Org. Lett. 2012, 14, 1834.
45. Wang, L.-L.; Lin, P.; Bai, J.-F.; Jia, L.-N.; Luo, X.-Y.; Huang, Q.-C.; Xu, X.-Y.;* Wang, L.-X.* Chem. Commun., 2011, 47, 5593.
46. Yang, M.-C.;Peng, C.;* Huang, H.; Yang, L.; He, X.-H.; Huang, W.; Cui, H.-L.; He, G.; Han, B.* Org. Lett. 2017, 19, 6752.
47. Qi, L.-W.; Yang, Y.; Gui, Y.-Y.; Zhang, Y.; Chen, F.; Tian, F.; Peng, L.; Wang, L.-X.;* Org. Lett. 2014, 16, 6436.
48. Tan, B.; Candeias, N. R.; Barbas III, C. F.;* Nature Chem. 2011, 3, 473.
49. Sun, W.; Hong, L.; Zhu, G.; Wang, Z.; Wei, X.; Ni, J.;* Wang, R.* Org. Lett. 2014, 16, 544.
50. Chen, Y.-R.; Reddy, G. M.; Hsieh, K.-H.; Chen, K.-H.; Karanam, P.; Vagh, S. S.; Liou, Y.-C.; Lin, W.* Chem. Commun. 2018, 54, 12702.
51. Zhao, B.-O.; Du, D.-M.* Chem. Commun. 2016, 52, 6162.
52. Kang, J.-W.; Li, X.; Chen, F.-Y.; Luo, Y.; Zhang, S.-C.; Kang, B.; Peng, C.; Tian, X.;* Han, B.* RSC Adv. 2019, 9, 12255.
53. Guo, H.-X.;* Wu, S.; Nadeau, K.; Moniz, G.A.; Caille, S. Chirality 2010, 22, 50.
54. Sibi, M. P.;* Rheault, T. R. J. Am. Chem. Soc. 2000, 122, 8873.

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